Role of hypothalamic interleukin-1β (IL-1β) in regulation of energy homeostasis by melanocortins

In the current study we sought to determine whether hypothalamic IL-1β is regulated by melanocortin signaling and if melanocortin-induced changes in energy balance are dependent on IL-1β. A melanocortin agonist, MTII, increased hypothalamic IL-1β mRNA levels by two-fold, whereas a melanocortin antagonist, SHU9119, blunted lipopolysaccharide (LPS)-mediated increase of hypothalamic IL-1β content. Pharmacological or genetic disruption of IL-1 receptor signaling prevented MTII-mediated reductions in locomotor activity, but did not reduce MTII-induced anorexia. These data suggest a potential role for central melanocortins in mediating the decrease of ambulation characteristic of the ‘sickness’ response.